Skip Navigation



Cardiovascular Research Advance Access [Accepted Manuscript] published online on June 3, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn138
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
79/4/621    most recent
cvn138v2
cvn138v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Farzaneh, T.
Right arrow Articles by Tinker, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Farzaneh, T.
Right arrow Articles by Tinker, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Differences in the mechanism of metabolic regulation of ATP-sensitive K+ channels containing Kir6.1 and Kir6.2 subunits

Tabasum Farzaneh and Andrew Tinker*

Room 107, The Rayne Institute, BHF Laboratories and Department of Medicine, University College London, 5 University Street, London, WC1E 6JJ

* Author for correspondence, Tel:- 020 7679 6391, Fax:- 020 7691 2838, e-mail:- a.tinker{at}ucl.ac.uk

Aims: ATP sensitive K+ channels (KATP) sense adenine nucleotide concentrations and thus couple the metabolic state of the cell to membrane potential. The hetero-octameric complex of a sulphonylurea receptor (SUR2B) and an inwardly rectifying K+ channel (Kir6.1) and the corresponding native channel in smooth muscle are relatively insensitive to variations in intracellular ATP. Activation of these channels in blood vessels during hypoxia/ischaemia is thought to be mediated via hormonal regulation such as cellular adenosine release or the release of mediators from the endothelium. In contrast intracellular ATP prominently inhibits Kir6.2 containing complexes, such as those present in cardiac myocytes. Thus we investigated differences in the mechanism of metabolic regulation of Kir6.1 and Kir6.2 containing KATP channels.

Methods and Results: We have heterologously expressed KATP channel subunits in HEK293 and CHO cells and studied their function using 86Rb efflux and patch clamping. We show that rodent Kir6.1/SUR2B has direct intrinsic metabolic sensitivity independent of any regulation by protein kinase A. In contrast to Kir6.2 containing complexes, this was not endowed by the ATP sensitivity of the pore forming subunit but was instead a property of the SUR2B subunit. Mutagenesis of key residues within the nucleotide binding domains implicated both domains in governing the metabolic sensitivity.

Conclusion: Kir6.1\SUR2B has intrinsic sensitivity to metabolism endowed by the likely processing of adenine nucleotides at the nucleotide binding domains of SUR2B.

Time for primary review: 25 days

Classification:- Experimental\vasculature\cellular\electrophysiology\ ion channels, ion transport, K-ATP channel, K-channel, smooth muscle


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.